Fresh or Not, Fecal Transplant Knocks Down C. Diff

Two studies bolster promise of microbiota replacement.

Action Points

Note that a small study demonstrated that frozen stool transplants may be as effective as fresh stool transplants for the treatment of C. difficile colitis.

An uncontrolled study of critically ill patients with C. diff colitis demonstrated that fecal transplant may help to avoid colectomy.

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be regarded as preliminary until they are published in a peer-reviewed journal.

PHILADELPHIA -- Fecal transplants are rapidly becoming a go-to procedure for patients with refractory Clostridium difficile infections, but researchers are still trying to work out the best approaches. Among the still unanswered questions: whether stool samples from healthy donors need to be fresh, and whether fecal transplants are effective in the severest infections where the patient's life may be at stake.

Frozen or lyophilized specimens may offer an effective and convenient alternative to fresh stool samples for fecal transplant in patients with recurrent episodes of Clostridium difficile infection, a researcher said here.

Among 13 patients with multiple episodes of C. difficile who were treated with fresh fecal samples, 92% were considered responders at 3 months, as were 93% of 15 patients who received frozen transplants, reported Zhi-Dong Jiang, MD, DPh, of the University of Texas in Houston.

In addition, 62% of patients who received freeze-dried samples also responded, for an overall 83% response rate.

Those rates included patients who had detectable Clostridium toxin in their stool at the time of fecal transplant. Among the patients who were toxin negative at the time of transplantation, 97% were considered responders, Jiang reported.

The study included 33 patients who had had three or more bouts of C. difficile. Prior to the fecal transplant, they were given a course of oral vancomycin.

Fecal samples were obtained from 10 carefully screened healthy donors, and were used within 2 hours if fresh and within 6 months if frozen or lyophilized. Analysis of the donor products determined that all formulations from an individual donor were similar in microbiota composition.

All treatments were given by colonoscopy.

At the time of transplant, two patients receiving the fresh transplant were positive for Clostridium toxin, as were four in the lyophilized group, and one in the frozen group.

One patient in each group developed a recurrence of C. difficile infection within a month of the transplant. Two of the patients with recurrences were positive for Clostridium toxin, and only one was toxin negative at the time of the transplant, the researcher noted.

There also was a "dramatic shift" in intestinal microbial flora, she noted. In comparison with samples of donor flora, which were characterized by abundant species of Firmicutes (64%) and Bacteroidetes (21.5%), recipients more often had Proteobacteria (62.3%) and fewer Firmicutes (31.76%).

However, after the transplant, only 6.8% of recipients still had dominant Proteobacteria, while 48.3% had Firmicutes and 24.5% had Bacteroidetes.

There also was an increase in the mucosal-related Verrucomicrobia, which was primarily driven by Akkermansia species. In recipient fecal samples obtained before and after the transplant, this increased from 0.054% to 12.12%.

"The mucosal-associated Akkermansia species may predict improvement in gut barrier function and mutualism between gut microbiota and host," she explained.

"Patients took on the microbial flora characteristics of the donors," commented Mark Mellow, MD, an internist in Oklahoma City who was involved in writing the college's guidelines on treating severe C. difficile infection.

"But the results also need to be confirmed in larger numbers of patients. A metabolomic analysis also would be useful, to look at enzymes and activity and see how the bacteria are doing their jobs," Mellow told MedPage Today.

"Being able to use frozen stool, or even to freeze-dry it and put it in a capsule for oral ingestion, would make it much easier to coordinate the donor and recipient," said John R. Saltzman, MD, director of endoscopy at Brigham and Women's Hospital in Boston, in a "virtual" press conference.

"Future studies are needed to clarify the active therapeutic properties in stools in the treatment of dysbiosis," Jiang concluded.

In the second study reported at the ACG meeting, critically ill patients responded to fecal microbiota transplantation.

Severe C. Diff: Fecal Transplant Saves Colon, Lives

Fecal microbiota transplantation was lifesaving for patients who were critically ill with Clostridium difficile infection, according to a small study also reported here.

Between July 2013 and April 2014, a total of 17 patients with severe or complicated C. diff infection who were being considered for urgent colectomy were offered fecal microbiota transplantation instead, and the overall cure rate was 88%, according to Monika Fischer, MD, of Indiana University in Indianapolis.

Severe C. diff infection can lead to fulminant colitis and multi-organ failure, and prompt subtotal colectomy may be needed, yet half of patients die following this procedure.

In recent years, fecal microbiota transplantation has become increasingly popular for recurrent C. diff infection, but there have been only a few case reports of this procedure being done in potentially lethal circumstances.

The patients' mean age was 68, slightly more than half were women, and all were white.

Severe and complicated C. diff infection was defined according to the college's 2013 guidelines, and all patient data and outcomes were collected prospectively.

The procedure involved carbon dioxide insufflation with a colonoscope, and the site of delivery of the transplanted material was determined by the endoscopist. This was proximal to the splenic flexure in 60% and distal in the others.

The fresh stool used was obtained from a donor chosen by the patient or from a "universal donor."

A total of 65% of the patients were given bowel preparation in advance of the transplant.

Six hours after the procedure, antibiotic treatment with oral vancomycin was initiated, given every 6 hours in doses of 125 mg for 5 to 14 days.

Ten patients received a second transplant, at a median time of 7.5 days after the first. For those who showed signs of pseudomembranous colitis at the time of the second transplant, vancomycin was continued and a third transplant was considered. The third transplant was done for three of those patients.

Fifteen of the patients were considered cured and were able to avoid colectomy for up to 3 months.

Two patients succumbed to multi-organ failure. One of these had recently undergone liver transplantation and was receiving immunosuppressive treatment, and the other had septic shock. There were no serious adverse events related to the procedure itself.

Mellow told MedPage Today that "this is an important paper because this patient population is at high risk for emergency colectomy, without which they could die."

"A study like this is complicated to do in the real world in the U.S.," said Mellow.

"You have to contact the FDA, as it's off label, and have frozen stool available because you wouldn't have enough time to adequately screen a donor. That requires 4 days or more, and these patients need something the day you see them," he said.

"As to whether a randomized trial is needed, I don't know. We have historical data on what happens to these patients without the fecal transplant. This study convinced me," Mellow said.

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